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Aeha -aha symposium-nov-2005-short


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Aeha -aha symposium-nov-2005-short

  1. 1. AHA- Nov 12, 2005 , Dallas P.K.Shah, MD Director of Cardiology and Atherosclerosis Research Center, Cedars-Sinai Medical Center, Professor of Medicine, David Geffen School of Medicine at UCLA Los Angeles, California Imperative to Detect Subclinical Atherosclerosis
  2. 2. Coronary Artery Disease 4 out of every 10 individuals who develop a heart attack or sudden death from coronary artery disease have no prior warning or symptoms
  3. 3. CVD Risk Assessment in Asymptomatic Normal Subjects Limitations of the Traditional Approach PKS- CSMC *One or more “Risk Factor” Accounts for 80-90% of CHD Events *Therefore Risk Factors can Predict most CHD Events
  4. 4. CVD Risk Assessment in Asymptomatic Normal Subjects Limitations of the Traditional Approach PKS- CSMC 0 10 20 30 40 50 60 70 80 90 100 Death Death/MI % with > 1 Risk Factors No Death/MINo Death men women
  5. 5. Pathophysiologic Paradigm in AtherosclerosisPathophysiologic Paradigm in Atherosclerosis Oxidant StressOxidant Stress Inflammatory Gene ActivationInflammatory Gene Activation AtherosclerosisAtherosclerosis Inflammatory Cell Recruitment/ActivationInflammatory Cell Recruitment/Activation Modified LDL Other mechanisms Other mechanisms Othermechanisms Other mechanisms Plaque-disruption/ThrombosisPlaque-disruption/Thrombosis Genes Genes Price M and Shah PK: Harrison’s Textbook of Medicne Online 2002 LDL , HDL , Diabetes-IRS-Metabolic Synd , Hypertension , Genetics, Others
  6. 6. Lipoproteins Entry into Subendothelial Space Lipoprotein Binding and Retention Lipoprotein Modification (oxidation) Inflammatory Gene Induction Inflammation Immune Activation Athero-prone sites
  7. 7. LDL with Reduced Binding Affinity to Subendothelial Matrix is Associated With Reduced Atherosclerosis Despite Severe Hypercholesterolemia Skalen K et al: Nature 417:750:2002 Defective LDL Normal LDL
  8. 8. CSMC--PKS 0 2 4 6 8 10 12 0 1 2 3 4 5 6 7 MyD88 +/+ +/- -/- Genotype Normal Partial Complete Deficiency Absence Cholesterol (mg/dl) 943 913 760 Cholesterol (mg/dl) 943 913 760 Genetic Ablation of Myeloid Differentiation Factor (MyD88) Reduces Atherosclerosis and Plaque Inflammation in Apo E Null Mice Despite Hypercholesterolemia P<0.01 P<0.01 % Macrophage Immunoreactivity% Aortic Surface with Plaque Michelsen, Wong, Shah, Arditi : PNAS 2004 MyD88 +/+ +/- -/- Genotype Normal Partial Complete Deficiency Absence
  9. 9. + Risk Factors + Disease + Events
  10. 10. Atherosclerosis And/or (Pre-atherosclerosis) Impaired Flow Dynamics Increased Stiffness Disease Activity (Biomarkers, Plaque Phenotype) Vaso-occlusive Clinical Events *EBCT *IMT *MRI Function Stress Test Endothelial Function*CRP,LP-PLA2 *Gene SNP , Proteomics *Plaque Composition
  11. 11. CVD Risk Assessment: A Different Paradigm Traditional Risk Factor Based Disease Modification Imaging for Identification of Subclinical Atherosclerosis EBCT-MSCT, Carotid IMT, MRI Non-invasive Assessment of Vascular Function BART, ABI, Compliance , Stress Test Markers for Disease Activity Inflammatory and other Biomarkers PKS- CSMC